The Proportion of Prostate-specific Antigen (PSA)
Complexed to
1
-Antichymotrypsin Improves the
Discrimination between Prostate Cancer and
Benign Prostatic Hyperplasia in Men with a Total
PSA of 10 to 30 g/L
ManuelMartı´nez,
1
Francisco Espan ˜ a,
2*
Montserrat Royo,
2
Jose ´ M. Alapont,
1
Silvia Navarro,
2
Amparo Estelle ´s,
2
Justo Aznar,
3
Ce ´sar D. Vera,
1
and
Juan F. Jime ´nez-Cruz
1
Background: The aim of this study was to assess the
diagnostic accuracy of the proportion of prostate-spe-
cific antigen (PSA) complexed to
1
-antichymotrypsin
(PSA-
1
ACT:PSA ratio) in the differential diagnosis of
prostate cancer (CaP) and benign prostatic hyperplasia
(BPH) in men with total PSA of 10 –30 g/L.
Methods: We used our immunoassays (ELISAs) for total
PSA and PSA-
1
ACT complex to study 146 men. In 123,
total PSA was between 10 and 20 g/L; 66 of these had
CaP and 57 BPH. In 23 men, total PSA was between 20
and 30 g/L; 14 of these had CaP and 9 BPH. We
calculated the area under the ROC curves (AUC) for
total PSA, PSA-
1
ACT complex, and PSA-
1
ACT:PSA
ratio, and determined the cutoff points that gave sensi-
tivities approaching 100%.
Results: In the total PSA range between 10 and 20 g/L,
the AUC was significantly higher for the PSA-
1
ACT:
PSA ratio (0.850) than for total PSA (0.507) and PSA-
1
ACT complex (0.710; P <0.0001). A cutoff ratio of 0.62
would have permitted diagnosis of all 66 patients with
CaP (100% sensitivity) and avoided 19% of unnecessary
biopsies (11 of 57 patients). In the total PSA range
between 20 and 30 g/L, the AUC for the PSA-
1
ACT:
PSA ratio (0.980; 95% confidence interval, 0.82– 0.99) was
greater than the AUC for total PSA (0.750; 95% confi-
dence interval, 0.51– 0.89; P 0.042). In this range, a
cutoff point of 0.64 would have permitted the correct
diagnosis of all 14 patients with CaP and 6 of the 9 with
BPH.
Conclusions: The diagnostic accuracy of the PSA-
1
ACT:PSA ratio persists at high total PSA concentra-
tions, increasing the specificity of total PSA. Prospective
studies with large numbers of patients are needed to
assess whether the ratio of PSA-
1
ACT to total PSA is a
useful tool to avoid unnecessary prostatic biopsy in
patients with a total PSA >10 g/L.
© 2002 American Association for Clinical Chemistry
The diagnostic accuracy of circulating prostate-specific
antigen (PSA)
4
for prostate cancer (CaP) is limited because
increases are not specific for CaP. Benign conditions of the
prostate influence its serum concentration; some patients
with benign prostatic hyperplasia (BPH) have increased
PSA (1), and many patients with clinically localized CaP
do not have increased serum PSA (2). Attempts to im-
prove the diagnostic accuracy of the PSA test include PSA
density (3, 4), PSA velocity (5), and age-specific reference
intervals (6), none of which has gained wide acceptance.
Active PSA forms complexes in vitro and in vivo with
1
-antichymotrypsin (
1
ACT),
2
-macroglobulin, protein
C inhibitor,
1
-protease inhibitor, and inter-
1
-trypsin
inhibitor (7–13 ). Measurement of the proportion of PSA
complexed to
1
ACT may increase the diagnostic accu-
racy of PSA testing for early CaP and avoid unnecessary
1
Department of Urology,
2
Research Center, and
3
Department of Clinical
Pathology, La Fe University Hospital, 46009 Valencia, Spain.
*Address correspondence to this author at: Hospital Universitario La Fe,
Centro de Investigacio ´ n, Avda. Campanar 21, 46009 Valencia, Spain. Fax
34-96-3868718; e-mail espanya_fra@gva.es.
Received January 8, 2002; accepted March 22, 2002.
4
Nonstandard abbreviations: PSA, prostate-specific antigen; CaP, prostate
cancer; BPH, benign prostatic hyperplasia;
1
ACT,
1
-antichymotrypsin; and
AUC, area under the ROC curve.
Clinical Chemistry 48:8
1251–1256 (2002)
Cancer Diagnostics:
Discovery and Clinical
Applications
1251
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